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Lithium response in bipolar disorder is associated with focal adhesion and PI3K-Akt networks: a multi-omics replication study.
Ou, Anna H; Rosenthal, Sara B; Adli, Mazda; Akiyama, Kazufumi; Akula, Nirmala; Alda, Martin; Amare, Azmeraw T; Ardau, Raffaella; Arias, Bárbara; Aubry, Jean-Michel; Backlund, Lena; Bauer, Michael; Baune, Bernhard T; Bellivier, Frank; Benabarre, Antonio; Bengesser, Susanne; Bhattacharjee, Abesh Kumar; Biernacka, Joanna M; Cervantes, Pablo; Chen, Guo-Bo; Chen, Hsi-Chung; Chillotti, Caterina; Cichon, Sven; Clark, Scott R; Colom, Francesc; Cousins, David A; Cruceanu, Cristiana; Czerski, Piotr M; Dantas, Clarissa R; Dayer, Alexandre; Del Zompo, Maria; Degenhardt, Franziska; DePaulo, J Raymond; Étain, Bruno; Falkai, Peter; Fellendorf, Frederike Tabea; Ferensztajn-Rochowiak, Ewa; Forstner, Andreas J; Frisén, Louise; Frye, Mark A; Fullerton, Janice M; Gard, Sébastien; Garnham, Julie S; Goes, Fernando S; Grigoroiu-Serbanescu, Maria; Grof, Paul; Gruber, Oliver; Hashimoto, Ryota; Hauser, Joanna; Heilbronner, Urs.
Affiliation
  • Ou AH; Department of Psychiatry, University of California San Diego, La Jolla, CA, USA.
  • Rosenthal SB; Center for Computational Biology and Bioinformatics, Department of Medicine, University of California San Diego, La Jolla, CA, USA.
  • Adli M; Department of Psychiatry and Psychotherapy, Charité- Universitätsmedizin Berlin, Campus Charité Mitte, Berlin, Germany.
  • Akiyama K; Fliedner Klinik Berlin, Center for Psychiatry, Psychotherapy and Psychosomatic Medicine, Berlin, Germany.
  • Akula N; Department of Biological Psychiatry and Neuroscience, Dokkyo Medical University School of Medicine, Mibu, Japan.
  • Alda M; Intramural Research Program, National Institute of Mental Health, National Institutes of Health, US Department of Health & Human Services, Bethesda, MD, USA.
  • Amare AT; Department of Psychiatry, Dalhousie University, Halifax, NS, Canada.
  • Ardau R; National Institute of Mental Health, Klecany, Czech Republic.
  • Arias B; Discipline of Psychiatry, University of Adelaide, Adelaide, SA, Australia.
  • Aubry JM; Unit of Clinical Pharmacology, Hospital University Agency of Cagliari, Cagliari, Italy.
  • Backlund L; Department of Evolutive Biology, Ecology and Environmental Sciences, Facultat de Biologia and Institut de Biomedicina (IBUB), Universitat de Barcelona, Barcelona, Spain.
  • Bauer M; CIBER de Salud Mental, ISCIII, Madrid, Barcelona, Catalonia, Spain.
  • Baune BT; Department of Mental Health and Psychiatry, Mood Disorders Unit-Geneva University Hospitals, Geneva, Switzerland.
  • Bellivier F; Department of Molecular Medicine and Surgery, Karolinska Institutet and Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden.
  • Benabarre A; Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Medical Faculty, Technische Universität Dresden, Dresden, Germany.
  • Bengesser S; Discipline of Psychiatry, University of Adelaide, Adelaide, SA, Australia.
  • Bhattacharjee AK; Department of Psychiatry, University of Münster, Münster, Germany.
  • Biernacka JM; INSERM UMR-S 1144-Université Paris Cité Département de Psychiatrie et de Médecine Addictologique, AP-HP, Groupe Hospitalier Lariboisière-F Widal, Paris, France.
  • Cervantes P; Bipolar and Depressive Disorders Unit, Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, ISCIII, Barcelona, Catalonia, Spain.
  • Chen GB; Neurobiological Background and Anthropometrics in Bipolar Affective Disorder, Division of Psychiatry and Psychotherapeutic Medicine, Medical University of Graz, Graz, Austria.
  • Chen HC; Department of Psychiatry, University of California San Diego, La Jolla, CA, USA.
  • Chillotti C; Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
  • Cichon S; Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, USA.
  • Clark SR; The Neuromodulation Unit, McGill University Health Centre, Montreal, QC, Canada.
  • Colom F; The Neuromodulation Unit, McGill University Health Centre, Montreal, QC, Canada.
  • Cousins DA; Department of Psychiatry & Center of Sleep Disorders, National Taiwan University Hospital, Taipei, Taiwan.
  • Cruceanu C; Unit of Clinical Pharmacology, Hospital University Agency of Cagliari, Cagliari, Italy.
  • Czerski PM; Institute of Human Genetics, University of Bonn and Department of Genomics, Life & Brain Center, Bonn, Germany.
  • Dantas CR; Human Genomics Research Group, Department of Biomedicine, University Hospital Basel, Basel, Switzerland.
  • Dayer A; Discipline of Psychiatry, University of Adelaide, Adelaide, SA, Australia.
  • Del Zompo M; Bipolar and Depressive Disorders Unit, Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, ISCIII, Barcelona, Catalonia, Spain.
  • Degenhardt F; Campus for Ageing and Vitality, Newcastle University, Newcastle upon Tyne, UK.
  • DePaulo JR; Douglas Mental Health University Institute, McGill University, Montreal, QC, Canada.
  • Étain B; Psychiatric Genetic Unit, Poznan University of Medical Sciences, Poznan, Poland.
  • Falkai P; Department of Psychiatry, University of Campinas (Unicamp), Campinas, Brazil.
  • Fellendorf FT; Department of Mental Health and Psychiatry, Mood Disorders Unit-Geneva University Hospitals, Geneva, Switzerland.
  • Ferensztajn-Rochowiak E; Unit of Clinical Pharmacology, Hospital University Agency of Cagliari, Cagliari, Italy.
  • Forstner AJ; Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy.
  • Frisén L; Institute of Human Genetics, University of Bonn and Department of Genomics, Life & Brain Center, Bonn, Germany.
  • Frye MA; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD, USA.
  • Fullerton JM; INSERM UMR-S 1144-Université Paris Cité Département de Psychiatrie et de Médecine Addictologique, AP-HP, Groupe Hospitalier Lariboisière-F Widal, Paris, France.
  • Gard S; Institute of Psychiatric Phenomics and Genomics (IPPG) and Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University of Munich, Munich, Germany.
  • Garnham JS; Neurobiological Background and Anthropometrics in Bipolar Affective Disorder, Division of Psychiatry and Psychotherapeutic Medicine, Medical University of Graz, Graz, Austria.
  • Goes FS; Department of Adult Psychiatry, Poznan University of Medical Sciences, Poznan, Poland.
  • Grigoroiu-Serbanescu M; Institute of Human Genetics, University of Bonn and Department of Genomics, Life & Brain Center, Bonn, Germany.
  • Grof P; Department of Molecular Medicine and Surgery, Karolinska Institutet and Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden.
  • Gruber O; Department of Clinical Neuroscience, Karolinska Institutet and Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden.
  • Hashimoto R; Child and Adolescent Psychiatry Research Center, Stockholm, Sweden.
  • Hauser J; Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, USA.
  • Heilbronner U; Mental Illness Research Theme, Neuroscience Research Australia, Sydney, NSW, Australia.
Transl Psychiatry ; 14(1): 109, 2024 Feb 23.
Article in En | MEDLINE | ID: mdl-38395906
ABSTRACT
Lithium is the gold standard treatment for bipolar disorder (BD). However, its mechanism of action is incompletely understood, and prediction of treatment outcomes is limited. In our previous multi-omics study of the Pharmacogenomics of Bipolar Disorder (PGBD) sample combining transcriptomic and genomic data, we found that focal adhesion, the extracellular matrix (ECM), and PI3K-Akt signaling networks were associated with response to lithium. In this study, we replicated the results of our previous study using network propagation methods in a genome-wide association study of an independent sample of 2039 patients from the International Consortium on Lithium Genetics (ConLiGen) study. We identified functional enrichment in focal adhesion and PI3K-Akt pathways, but we did not find an association with the ECM pathway. Our results suggest that deficits in the neuronal growth cone and PI3K-Akt signaling, but not in ECM proteins, may influence response to lithium in BD.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Bipolar Disorder / Lithium Limits: Humans Language: En Journal: Transl Psychiatry Year: 2024 Document type: Article Affiliation country:
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Bipolar Disorder / Lithium Limits: Humans Language: En Journal: Transl Psychiatry Year: 2024 Document type: Article Affiliation country: